B lymphocyte recognition of the self antigen mouse cytochrome C in different mouse strains: targeting of the same dominant epitope by naturally-occurring cells expressing distinct VH genes.
Previously we reported that, early in the antibody response of BALB/c mice to several cytochromes c (CYT) coupled to ovalbumin (OVA), B cells responding to the self antigen mouse CYT recognized a single site on mouse CYT and were in much higher frequency than B cells responding to foreign CYT. In the present study these B cells were shown by in vitro activation of primary splenocytes to be present in naive BALB/c mice, i.e. prior to exposure to exogenous CYT. The higher frequency of B cells responsive to self versus foreign CYT was also shown in this study to occur in the early antibody response to CYT-OVA in C57BL/6 mice. The same dominant site was recognized in BALB/c mice (IgHa), C57BL/6 mice (IgHb) and the congenic strains BC-17 (IgHa on the C57BL/6 background) and CB-20 (IgHb on the BALB/c background). However, anti-mouse CYT mAbs produced in IgHb mice were shown to derive from the VH gene 5.54.4 while mAbs in IgHa mice derive from the VH gene 19.1.2. The polypeptides encoded by these VH genes, which differ by only five amino acid residues, paired with polypeptides encoded by the same Vk genes (R9 and 2G5). In both VH 19.1.2- and VH 5.54.4-derived mAbs H3 and the Vk-Jk join were variable. The affinity for mouse CYT was reduced in the VH gene 5.54.4-derived mAb due to a faster off-rate constant. This difference in affinity may relate to the lower frequency of B cells responding to mouse CYT in C57BL/6 mice than in BALB/c mice. The results show that naturally-occurring CYT-specific autoreactive B cells occur normally in more than one mouse strain and that self antigen recognition by those cells appears to be atypical involving mostly the immunoglobulin V gene-encoded segments.
Mueller
C M
CM
Department of Microbiology and Center for Immunology, University of Minnesota Medical School, Minneapolis 55455, USA.
Minnerath
J M
JM
Jemmerson
R
R
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D002478:Cells, Cultured; D010856:Columbidae; D003574:Cytochrome c Group / Q000276:immunology*; D006736:Horses; D016056:Immunodominant Epitopes / Q000276:immunology*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics* / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011817:Rabbits; D051381:Rats; D017634:Self Tolerance / Q000276:immunology*; D014413:Tuna
D003574:Cytochrome c Group; D016056:Immunodominant Epitopes; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region